This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. One of the complications of diabetes is the production of excess reactive oxygen species (ROS) in cells. ROS are highly reactive oxygen-containing molecules that can damage proteins or nucleic acids thereby resulting in cell death or abnormal function. Excess ROS are particularly harmful for cardiovascular tissues. ROS are produced as by products of proteins which metabolize glucose and are generally not a problem in individuals with normal blood glucose. In diabetic individuals however, these metabolizing enzymes are overwhelmed and excess ROS results. A cell normally has mechanisms to counteract excess ROS production including nitric oxide (NO), whose levels are inversely proportional to ROS. In diabetic conditions however, NO levels are also decreased which enhances the possibility of oxidative damage. In this project therefore we will utilize mouse models of diabetes and explore mechanisms to counteract high ROS levels.